6-85450239-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002526.4(NT5E):āc.100A>Gā(p.Thr34Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,457,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
NT5E
NM_002526.4 missense
NM_002526.4 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 5.14
Genes affected
NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.925
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NT5E | NM_002526.4 | c.100A>G | p.Thr34Ala | missense_variant | 1/9 | ENST00000257770.8 | NP_002517.1 | |
NT5E | NM_001204813.2 | c.100A>G | p.Thr34Ala | missense_variant | 1/8 | NP_001191742.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NT5E | ENST00000257770.8 | c.100A>G | p.Thr34Ala | missense_variant | 1/9 | 1 | NM_002526.4 | ENSP00000257770.3 | ||
NT5E | ENST00000369646.7 | c.100A>G | p.Thr34Ala | missense_variant | 1/3 | 1 | ENSP00000358660.3 | |||
NT5E | ENST00000369651.7 | c.100A>G | p.Thr34Ala | missense_variant | 1/8 | 2 | ENSP00000358665.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1457870Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 725038
GnomAD4 exome
AF:
AC:
6
AN:
1457870
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
725038
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2023 | The c.100A>G (p.T34A) alteration is located in exon 1 (coding exon 1) of the NT5E gene. This alteration results from a A to G substitution at nucleotide position 100, causing the threonine (T) at amino acid position 34 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
Loss of catalytic residue at T34 (P = 0.1106);Loss of catalytic residue at T34 (P = 0.1106);Loss of catalytic residue at T34 (P = 0.1106);
MVP
MPC
0.69
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at